RANTES production in nasal epithelial cells and endothelial cells

Background: It is well documented that the chemokine that is regulated upon activation, normal T expressed and presumably secreted, RANTES, is produced by macrophages, platelets, fibroblasts, and renal tubular epithelial cells. Recently, however, production of RANTES by vascular endothelium and airway epithelial cells was demonstrated in human umbilical vein endothelial cells (HUVECs) and epithelial cell lines. Objective: This investigation was aimed at determining whether human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs) produce RANTES when they are stimulated by several cytokines. Methods: HNECs nd HMMECs were isolated from nasal mucosa and subsequent continuous subcultures and were stimulated either by IL-1 beta or by the combination of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Results: After the combined stimulation by TNF-alpha and IFN-gamma, HNECs and HMMECs dramatically produced RANTES, as previously observed in HUVECs and bronchial epithelial cell line BEAS-2B. IL-1 beta also increased RANTES production to a lesser extent. We also demonstrated that the amount of RANTES induced by TNF-alpha and IFN-gamma was higher in HNECs and HMMECs obtained from patients with nasal allergy than in those from patients without allergy. Conclusion: RANTES from HNECs and HMMECs likely plays a critical role in eosinophil infiltration of the nasal mucosa in subjects with nasal allergy.